Motor Unit Magnetic Resonance Imaging (MUMRI) In Skeletal Muscle

\ua9 2024 The Authors. Journal of Magnetic Resonance Imaging published by Wiley Periodicals LLC on behalf of International Society for Magnetic Resonance in Medicine.Magnetic resonance imaging (MRI) is routinely used in the musculoskeletal system to measure skeletal muscle structure and pathology in health and disease. Recently, it has been shown that MRI also has promise for detecting the functional changes, which occur in muscles, commonly associated with a range of neuromuscular disorders. This review focuses on novel adaptations of MRI, which can detect the activity of the functional sub-units of skeletal muscle, the motor units, referred to as “motor unit MRI (MUMRI).” MUMRI utilizes pulsed gradient spin echo, pulsed gradient stimulated echo and phase contrast MRI sequences and has, so far, been used to investigate spontaneous motor unit activity (fasciculation) and used in combination with electrical nerve stimulation to study motor unit morphology and muscle twitch dynamics. Through detection of disease driven changes in motor unit activity, MUMRI shows promise as a tool to aid in both earlier diagnosis of neuromuscular disorders and to help in furthering our understanding of the underlying mechanisms, which proceed gross structural and anatomical changes within diseased muscle. Here, we summarize evidence for the use of MUMRI in neuromuscular disorders and discuss what future research is required to translate MUMRI toward clinical practice. Level of Evidence: 5. Technical Efficacy: Stage 3

Whole-body fasciculation detection in amyotrophic lateral sclerosis using motor unit MRI (MUMRI)

\ua9 2024 International Federation of Clinical NeurophysiologyObjective: Compare fasciculation rates between amyotrophic lateral sclerosis (ALS) patients and healthy controls in body regions relevant for diagnosing ALS using motor unit MRI (MUMRI) at baseline and 6 months follow-up, and relate this to single-channel surface EMG (SEMG). Methods: Tongue, biceps brachii, paraspinals and lower legs were assessed with MUMRI and biceps brachii and soleus with SEMG in 10 healthy controls and 10 patients (9 typical ALS, 1 primary lateral sclerosis [PLS]). Results: MUMRI-detected fasciculation rates in typical ALS patients were higher compared to healthy controls for biceps brachii (2.40 \ub1 1.90 cm-3min−1 vs. 0.04 \ub1 0.10 cm-3min−1, p = 0.004), paraspinals (1.14 \ub1 1.61 cm-3min−1 vs. 0.02 \ub1 0.02 cm-3min−1, p = 0.016) and lower legs (1.42 \ub1 1.27 cm-3min−1 vs. 0.13 \ub1 0.10 cm-3min−1, p = 0.004), but not tongue (1.41 \ub1 1.94 cm-3min−1 vs. 0.18 \ub1 0.18 cm-3min−1, p = 0.556). The PLS patient showed no fasciculation. At baseline, 6/9 ALS patients had increased fasciculation rates compared to healthy controls in at least 2 body regions. At follow-up every patient had increased fasciculation rates in at least 2 body regions. The MUMRI-detected fasciculation rate correlated with SEMG-detected fasciculation rates (τ = 0.475, p = 0.006). Conclusion: MUMRI can non-invasively image fasciculation in multiple body regions and appears sensitive to disease progression in individual patients. Significance: MUMRI has potential as diagnostic tool for ALS

Vortex deformation and breaking in superconductors: A microscopic description

Vortex breaking has been traditionally studied for nonuniform critical current densities, although it may also appear due to nonuniform pinning force distributions. In this article we study the case of a high-pinning/low-pinning/high-pinning layered structure. We have developed an elastic model for describing the deformation of a vortex in these systems in the presence of a uniform transport current density $J$ for any arbitrary orientation of the transport current and the magnetic field. If $J$ is above a certain critical value, $J_c$, the vortex breaks and a finite effective resistance appears. Our model can be applied to some experimental configurations where vortex breaking naturally exists. This is the case for YBa$_2$Cu$_3$O$_{7-x}$ (YBCO) low angle grain boundaries and films on vicinal substrates, where the breaking is experienced by Abrikosov-Josephson vortices (AJV) and Josephson string vortices (SV), respectively. With our model, we have experimentally extracted some intrinsic parameters of the AJV and SV, such as the line tension $\epsilon_l$ and compared it to existing predictions based on the vortex structure.Comment: 11 figures in 13 files; minor changes after printing proof

Effect of Standard vs Intensive Blood Pressure Control on Cerebral Blood Flow in Small Vessel Disease The PRESERVE Randomized Clinical Trial

Importance: Blood pressure lowering is considered neuroprotective in patients with cerebral small vessel disease, however more “intensive” regimens may increase cerebral hypoperfusion. We examined the effect of intensive vs. standard blood pressure treatment on cerebral perfusion in severe small vessel disease patients. Objective: To determine whether intensive vs. standard blood pressure lowering over 3 months causes decreased cerebral perfusion. Design, Setting and Participants: This randomised, parallel, controlled, blinded-outcomes clinical trial took place in 2 English university medical centres. A central, online randomisation system (1:1 ratio) allocated grouping. 70 hypertensive patients with MRI confirmed symptomatic lacunar infarct and confluent white matter hyperintensities were recruited between 2012 and 2015, and randomised (36/34 in standard/intensive arms). Analysable data were available in 62 patients, 33/29 in the standard/intensive groups respectively, for intention to treat analysis. This experiment examines the 3 month follow-up period. Intervention: Patients were randomised to “standard” (systolic=130-140mmHg) or “intensive” (systolic=<125mmHg) blood pressure targets, to be achieved through medication regimen changes. Main Outcome and Measure: Cerebral perfusion was determined using arterial spin labelling; the primary end point was change in global perfusion between baseline and 3 months, compared between treatment groups by ANOVA. Linear regression compared change in perfusion against change in blood pressure. MR scan analysis was blinded to treatment arm. Results: Patients were 69.3 years old (mean) and 59.7% male. Mean(SD) systolic blood pressure reduced by 8(12) and 27(17)mmHg in the standard/intensive groups, respectively (p<0.001), with achieved pressures of 141(13) and 126(10) mmHg respectively. Change in global perfusion did not differ between treatment arms: standard, mean(SD) (ml/min/100g)= -0.5(9.4); intensive, 0.7(8.6), partial ETA2= 0.004, 95% CI= -3.6–5.8, p= 0.63. No differences were observed when analysis examined grey/white matter only, or was confined to those achieving target blood pressure. The number of adverse events did not differ between treatment groups (standard/intensive mean(SD)= .21(.65)/.32(.75), p=.44). Conclusions and Relevance: Intensive blood pressure lowering did not reduce cerebral perfusion in severe small vessel disease.This study was funded by a joint Stroke Association/British Heart Foundation program grant (TSA BHF 2010/01). The study received additional support from the Newcastle Biomedical Research Centre, which is funded by the National Institute for Health Research (NIHR). Drs O’Brien, Ford, and Markus are supported by NIHR Senior Investigator awards. Drs O’Brien and Markus are also supported by the Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre

Using DTI to assess white matter microstructure in cerebral small vessel disease (SVD) in multicentre studies

Diffusion tensor imaging (DTI) metrics such as fractional anisotropy (FA) and mean diffusivity (MD) have been proposed as clinical trial markers of cerebral small vessel disease (SVD) due to their associations with outcomes such as cognition. However, studies investigating this have been predominantly single-centre. As clinical trials are likely to be multisite, further studies are required to determine whether associations with cognition of similar strengths can be detected in a multicentre setting. One hundred and nine patients (mean age =68 years) with symptomatic lacunar infarction and confluent white matter hyperintensities (WMH) on MRI was recruited across six sites as part of the PRESERVE DTI substudy. After handling missing data, 3T-MRI scanning was available from five sites on five scanner models (Siemens and Philips), alongside neuropsychological and quality of life (QoL) assessments. FA median and MD peak height were extracted from DTI histogram analysis. Multiple linear regressions were performed, including normalized brain volume, WMH lesion load, and n° lacunes as covariates, to investigate the association of FA and MD with cognition and QoL. DTI metrics from all white matter were significantly associated with global cognition (standardized β =0.268), mental flexibility (β =0.306), verbal fluency (β =0.376), and Montreal Cognitive Assessment (MoCA) (β =0.273). The magnitudes of these associations were comparable with those previously reported from single-centre studies found in a systematic literature review. In this multicentre study, we confirmed associations between DTI parameters and cognition, which were similar in strength to those found in previous single-centre studies. The present study supports the use of DTI metrics as biomarkers of disease progression in multicentre studies.This work was supported by the British Heart Foundation and the Stroke Association [grant number TSA BHF 2010/01]; the NIHR-funded Newcastle Biomedical Research Centre; the NIHR Senior Investigator Awards (for H.S.M., J.T.O. and G.A.F.); and the Cambridge University Hospitals NIHR Comprehensive Biomedical Research Centre (for H.S.M. and J.T.O.)

PRESERVE: Randomized Trial of Intensive Versus Standard Blood Pressure Control in Small Vessel Disease.

Background and Purpose: In cerebral small vessel disease, cerebral blood flow and autoregulation are impaired and therefore excessive blood pressure reduction could possibly accelerate white matter damage and worsen outcome. The trial determined, in severe symptomatic cerebral small vessel disease, whether intensive blood pressure lowering resulted in progression of white matter damage assessed using diffusion tensor imaging. Methods: Randomized, parallel, multicenter controlled, blinded-outcomes clinical trial. One hundred eleven participants with magnetic resonance imaging confirmed symptomatic lacunar infarct and confluent white matter hyperintensities and were recruited and randomized to standard (systolic=130–140 mmHg) (N=56) or intensive (systolic<125 mmHg) (N=55) blood pressure targets. The primary end point was change in diffusion tensor imaging white matter mean diffusivity peak height between baseline and 24 months. Secondary end points were other magnetic resonance imaging markers and cognition. Results: Patients were mean 68 years and 60% male. Mean (SD) blood pressure reduced by −15.3 (15.4) and −23.1 (22.04) mm Hg in the standard/intensive groups, respectively (P<0.001). There was no difference between treatment groups for the primary end point: standard, adjusted mean (SE)=12.5×10−3 (0.2×10−3); intensive, 12.5×10−3 (0.2×10−3), P=0.92. In the whole population over 24 months follow-up, there was a significant deterioration in white matter microstructure but no detectable decrease in cognition. Conclusions: Intensive blood pressure lowering in severe cerebral small vessel disease was not associated with progression of white matter damage on diffusion tensor imaging or magnetic resonance imaging. In a multicentre study setting over 2 years, multimodal diffusion tensor imaging-magnetic resonance imaging was more sensitive to detecting change than cognitive testing